Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

EJNMMI Radiopharmacy and Chemistry

Table 4 Example release criteria clinical patient batch

Parameter	Quality control technique	Release criteria (based upon literature)
Preliminary release
Clear solution?	Visually	No particles visible
RCY	Radio-TLC Gamma counter HP-Ge detector	> 95%
Radionuclide identification	HP-Ge detector	Presence Fr-221/Bi-213
pH	Indicator paper	Between 5.5 and 9
Final activity	Dose calibrator Gamma counter	Patient dose ± 5%
Endotoxins	Endosafe PTS system	< 5 EU/mL
Filter integrity	Filter integrity test	Passed
Final release
RCP	HPLC/fraction measurement (gamma counter)	> 90%* up to 3 h

*In the risk-analysis, the RCP is discussed and resulted in a release criterion of the HPLC of 90%, here the risk of the 5% decrease was accepted, based on toxicity calculations and distribution of unlabelled Ac-225 is based on; 1. The unbound Ac-225 is complexed for 25% with DTPA and excreted by the kidneys (ICRP 2015). 2. 25% remains unbound (ICRP-30) and 3. 50% will be bound to PSMA metabolites (ICRP128 model for F-18 amino acids)